title: Vaccination with photodynamic therapy-treated macrophages induces highly suppressive T-regulatory cells.
abstract: OBJECTIVE
  The present study explores whether photodynamic therapy (PDT)-induced apoptosis can increase the number of tolerogenic regulatory T cells (Treg) and limit collateral tissue damage.
  
  
  METHODS
  BALB/c mice were vaccinated subcutaneously three times with PDT-induced apoptotic or thaw-frozen, necrotic non-infected autologous macrophages (MΦ). Two weeks after the last vaccination, mice were infected intradermally with 10(6) promastigotes of Leishmania major.
  
  
  RESULTS
  Mice that received PDT-induced apoptotic MΦ had fewer parasites and higher numbers of Treg than mice vaccinated with thaw-frozen necrotic MΦ or phosphate-buffered saline (PBS). Interleukin (IL)-4 and IL-6 were significantly suppressed, while IL-10 was increased in mice that received the PDT-induced apoptotic MΦ. The role of Treg in this process was confirmed through Treg transfer from vaccinated to naïve mice. Mice receiving CD4(+) CD25(+) cells from mice vaccinated with PDT-induced apoptotic MΦ showed smaller lesions 3 weeks after infection and lower parasitic burdens than mice that received Tregs from mice of thaw-frozen necrotic MΦ or PBS groups. These changes were mediated by the depletion of CD3(+) CD8(+) and NKT cells and increased levels of IL-12p70 and interferon-γ, IL-10, and TGF-β in the cutaneous leishmaniasis lesions.
  
  
  CONCLUSIONS
  Vaccination with apoptotic MΦ-induced tolerogenic Treg cells that limited collateral tissue damage and diminished parasitic burden.
authors.affiliation: Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. oea2@pitt.edu
authors.forename: Oleg E
authors.initials: OE
authors.lastname: Akilov
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
authors.forename: Yongzhu
authors.initials: Y
authors.lastname: Jin
authors.forename: Zhuoyan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Larisa J
authors.initials: LJ
authors.lastname: Geskin
authors.forename: Louis D
authors.initials: LD
authors.lastname: Falo
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000818:Animals; D017209:Apoptosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*